KCNN4-mediated Ca2+/MET/AKT axis is promising for targeted therapy of pancreatic ductal adenocarcinoma

• 作者: Xiao Mo Cheng-fei Zhang Ping Xu Min Ding Zhi-jie Ma Qi Sun Yu Liu Hong-kai Bi Xin Guo Alaa Abdelatty Chao Hu Hao-jun Xu Guo-ren Zhou Yu-liang Jia Hong-ping Xia
• 来源期刊: 中国药理学报（英文版）
• 年，卷（期）: 2022,（3）
• 所属期刊栏目: Chemotherapy
• 页码范围: 735-746
• 页数: 12页
• 语种: 英文

摘要

As a member of the potassium calcium-activated channel subfamily,increasing evidence suggests that KCNN4 was associated with malignancies.However,the roles and regulatory mechanisms of KCNN4 in PDAC have been little explored.In this work,we demonstrated that the level of KCNN4 in PDAC was abnormally elevated,and the overexpression of KCNN4 was induced by transcription factor AP-1.KCNN4 was closely correlated with unfavorable clinicopathologic characteristics and poor survival.Functionally,we found that overexpression of KCNN4 promoted PDAC cell proliferation,migration and invasion.Conversely,the knockdown of KCNN4 attenuated the growth and motility of PDAC cells.In addition to these,knockdown of KCNN4 promoted PDAC cell apoptosis and led to cell cycle arrest in the S phase.In mechanistic investigations,RNA-sequence revealed that the MET-mediated AKT axis was essential for KCNN4,encouraging PDAC cell proliferation and migration.Collectively,these findings reveal a function of KCNN4 in PDAC and suggest it's an attractive therapeutic target and tumor marker.Our studies underscore a better understanding of the biological mechanism of KCNN4 in PDAC and suggest novel strategies for cancer therapy.